The inheritance of 2 diabetes and obesity is likely determined by multiple genes. Consequently, the effect of a single susceptibility gene could be small and remain obscured in family-based linkage studies. To complement our genome-wide linkage studies of diabetes and obesity in the Pima Indians, we are therefore undertaking a genomic association scan by utilizing the AFLP technique for analysis of pooled DNA from subjects that represent the extremes of various phenotypes. AFLP is a PCR-based DNA fingerprinting method that allows simultaneous analysis of multiple random polymorphisms. Currently, studies are in progress to achieve a 1 cM resolution using relatively large DNA pools (up to 30 individuals per pool) from subjects with an early onset of diabetes (<25 years) vs non-diabetic controls (<45 years), as well as pools representing obese non-diabetic Pimas with high body mass index (BMI) vs lean Pimas with low BMI.